´
H. Sladowska et al. / Il Farmaco 57 (2002) 897Á
/
908
907
Table 7
Influence of the investigated compounds on the spontaneous locomo-
tor activity in mice
tion did not influence the toxicity of the mentioned
compounds. All had LD ꢀ2000 mg/kg.
/
5
0
Comp. Dose (mg/ % inhibition of locomotor
activity
ED50 (mg/kg)
kg)
5
. Conclusion
8
9
200
36.9
23.5
1
00
200
00
The analgesic action of new derivatives of 1H-
84.4***
45.8
107.9 (91Á121)
/
pyrrolo[3,4-c]pyridine-1,3(2H)-dione was investigated
on mice, using the ‘hot-plate’ and ‘writhing’ tests. All
of the compounds studied exhibited analgesic activity
which was superior to that of acetylsalicylic acid in the
both tests. Furthermore they caused significant suppres-
sion of the spontaneous locomotor activity in mice.
It is accepted that analgesics are generally considered
to act centrally, peripherally or both centrally and
peripherally. Narcotic analgesics such as morphine
produce their analgesic actions by a central mechanism,
but non-steroidal antiinflammatory agents, such as
aspirin-by a peripheral mechanism [19]. However, it is
supposed that salicylates produce their analgesic effects
partly by a central mechanism [20].
1
5
2
0
5
38.6
38.4
10
11
12
50
84.9***
73.3**
64.3*
82.9***
76.0**
68.7*
64.5***
58.3***
39.9*
34.1
6.15 (3.8Á8.2)
/
2
1
5
2.5
50
7.2 (5.1Á10.4)
/
2
1
5
2.5
50
19.7 (15.2Á23.3)
/
2
1
5
2.5
6
.25
Each group consisted of 6Á8 animals.
/
*
*
*
p B0.05.
* p B0.02.
** p ꢀ0.01.
Our results suggest that the investigated compounds
can show analgesic activity across central and peripheral
mechanism. The explanation of the exact mechanism of
action will demand of the further pharmacological
investigations.
N-4 of piperazine in the compound 8 (imides 10 and 11)
also weakens the analgesic properties, more in case of
11. Similar relationship was observed in the case of the
compounds 9 and 12.
Among the five studied substances the compound 12
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with OC H group in 4 and CF3 one in the meta
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was comparable with that of morphine. Contrary to
this, imide 12 was (apart from 8) the most active
substance in the ‘hot-plate’ test. Compound 11 contai-
ning in its structure two methoxy groups was endowed
with the weakest analgesic properties in this test.
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[
0
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50
Besten, L. Brandsma, D. Leysen, J. Kelder, Structure and